Collagen matricryptin promotes cardiac function by mediating scar formation.

AIMS: A peptide mimetic of a collagen-derived matricryptin (p1159) was shown to reduce left ventricular (LV) dilation and fibrosis after 7 days delivery in a mouse model of myocardial infarction (MI). This suggested p1159 long-term treatment post-MI could have beneficial effects and reduce/prevent adverse LV remodeling. This study aimed to test the potential of p1159 to reduce adverse cardiac remodeling in a chronic MI model and to elucidate p1159 mode-of-action. MATERIALS AND METHODS: Using a permanent occlusion MI rodent model, animals received p1159 or vehicle solution up to 28 days. We assessed peptide treatment effects on scar composition and structure and on systolic function. To assess peptide effects on scar vascularization, a cohort of mice were injected with Griffonia simplicifolia isolectin-B4. To investigate p1159 mode-of-action, LV fibroblasts from naïve animals were treated with increasing doses of p1159. KEY FINDINGS: Matricryptin p1159 significantly improved systolic function post-MI (2-fold greater EF compared to controls) by reducing left ventricular dilation and inducing the formation of a compliant and organized infarct scar, which promoted LV contractility and preserved the structural integrity of the heart. Specifically, infarcted scars from p1159-treated animals displayed collagen fibers aligned parallel to the epicardium, to resist circumferential stretching, with reduced levels of cross-linking, and improved tissue perfusion. In addition, we found that p1159 increases cardiac fibroblast migration by activating RhoA pathways via the membrane receptor integrin α4. SIGNIFICANCE: Our data indicate p1159 treatment reduced adverse LV remodeling post-MI by modulating the deposition, arrangement, and perfusion of the fibrotic scar.

AMP-activated protein kinase inhibits vascular smooth muscle cell proliferation and migration and vascular remodeling following injury.

Vascular smooth muscle cell (VSMC) activation promotes a synthetic phenotype that underlies many vessel growth disorders. In this regard it has been suggested that the metabolic sensor adenosine 5'-monophosphate-activated protein kinase (AMPK) has significant antigrowth and antimetastatic properties and may serve as a viable therapeutic target. In the current study we hypothesized that AMPK reduces neointima formation following balloon injury and that this occurs through reduction in VSMC proliferation and migration. Data reveal that local or systemic dosing with the AMPK agonist 5-aminoimidazole-4-carboxamide-1-ß-d-ribofuranoside (AICAR) significantly increased AMPK activity in vivo and inhibited neointima formation in rat carotid arteries 2 wk after injury. In primary VSMCs, AICAR inhibited migration and induced cytostatic growth arrest through increased protein phosphatase 2A-mediated inhibition of mitosis-promoting cyclin B. AICAR also significantly enhanced AMPK-specific T278 phosphorylation of the actin anticapping vasodilator-activated serum phosphoprotein, increased G- to F-actin ratios and stress fiber formation, and abrogated PDGF-stimulated S397 autophosphorylation of focal adhesion kinase, promigratory cytoplasmic accumulation of paxillin, and extracellular matrix proteolysis by matrix metalloproteinase-9. Together, these results provide compelling evidence that AMPK serves to inhibit vascular smooth muscle migration and proliferation through regulation of cytoskeletal/focal adhesion/ECM stability, increasing our knowledge of this important metabolic regulator and providing support for its continued investigation in the treatment of vascular growth disorders.

Giant condyloma acuminatum quickly growing: case report.

BACKGROUND: Giant Condyloma Acuminatum (GCA) is a rare, slow growing, large cauliflower tumor of the penile foreskin and perianal region with benign histologic appearance but high propensity for local invasion and recurrences. GCA is associated with Human Papilloma Virus (HPV) types 6 and 11 and it also has considerable risk of neoplastic transformation into fully invasive squamous cell carcinoma into about 5 years. OBJECTIVE: Because of the rarity of perianal GCA, to date there is no general agreement on the best method for treatment. We wanted to know if surgical approach only was a good method to treat our case. CASE REPORT: A 28 years old man, HIV-negative, with a 4 years history of perianal GCA quickly growing underwent full tickness local excision at least 0,7 cm margin of normal tissue with skin grafting taken from the thighs. Fecal contamination was avoided by diet and loperamide per os. At two years follow-up no recurrence was detected. CONCLUSION: Surgical approach with full tickness excision and immediate skin-grafting and regular follow-up demonstrated effective to treat GCA and to minimize disease recurrence.

A randomized pilot study of systemic immunosuppression in the treatment of age-related macular degeneration with choroidal neovascularization.

BACKGROUND: Age-related macular degeneration remains the leading cause of irreversible blindness in the United States and the developed world. Intravitreal injections of anti­vascular endothelial growth factor (VEGF) medications have become standard of care for the treatment of the wet form of the disease. Recent reports have demonstrated an association with various immune factors. We aimed to investigate the effect of immunosuppressive therapy in the clinical course of the wet form of the disease. We compared anti-VEGF therapy plus one of three systemic immunosuppressive therapies versus anti-VEGF therapy alone for recurrent choroidal neovascularization associated with age-related macular degeneration. METHODS: This was a pilot, Phase I/II, prospective, randomized, unmasked, single-center trial. Patients with subretinal exudation secondary to recurrent choroidal neovascularization associated with age-related macular degeneration were included in the study. Patients were randomized to 1 of 3 systemic arms immunosuppressive agents (daclizumab, rapamycin, or infliximab) for 6 months plus intraocular anti-VEGF therapy if indicated, compared with a group who received only anti-VEGF therapy if indicated. RESULTS: The number of anti-VEGF injections per group, visual acuity, retinal thickness, and safety measures were assessed in all groups. Thirteen patients were randomized; comparing anti-VEGF injections before and during the study, a decrease in the number of injections from 0.73 injections per month to 0.42 for daclizumab and from 0.67 to 0.34 for sirolimus was seen, while no apparent decrease was seen for either infliximab or observation. Visual acuities were maintained in all groups. CONCLUSION: These preliminary data suggest that some immunosuppressive agents given systemically can alter the clinical course of the wet form of the disease and support the notion that more definitive clinical trials of immune mediation of age-related macular degeneration are indicated.

Fissurectomy combined with anoplasty and injection of botulinum toxin in treatment of anterior chronic anal fissure with hypertonia of internal anal sphincter: a pilot study.

BACKGROUND: In patients affected by anterior chronic anal fissure (CAAF) with hypertonia of the internal anal sphincter (IAS), the role of IAS hypertonia remains unclear. The aim of this study was to evaluate the efficacy of fissurectomy combined with advancement flap and IAS injection of botulinum toxin in healing the CAAF with hypertonia of IAS resistant to medical therapy. METHODS: Ten consecutive patients were enrolled. Anorectal manometry was performed preoperatively and at 6 months. CAAF with hypertonia was defined as those associated with maximum resting pressure (MRP) values higher than 85 mmHg. All patients underwent fissurectomy and anoplasty with advancement skin flap combined with the intrasphincter injection of 30 UI of botulinum toxin. Complete healing, MRP changes, relief of symptoms and immediate and long-term complications were recorded. RESULTS: Complete healing was observed in all patients within 30 days of the operation. The intensity and duration of pain post-defecation was reduced significantly starting from the first defecation. In all subjects, the preoperative MRP values were significantly reduced at 6 months. One month after surgery, three patients reported anal incontinence, two of them had complained preoperatively. The only postoperative complications were minor. CONCLUSIONS: Fissurectomy combined with advancement flap and intrasphincter injection of botulinum toxin results in complete healing, significant MRP reduction and full relief of symptom in all patients, thus it represents a valid procedure in preventing the occurrence of anal incontinence.

Fissurectomy and anal advancement flap for anterior chronic anal fissure without hypertonia of the internal anal sphincter in females.

AIM: Lateral internal sphincterotomy is considered the surgical treatment of choice for chronic anal fissure after failure of medical therapy but it risks continence. The aim of the study was to evaluate fissurectomy with advancement flap for anterior chronic anal fissure (CAAF) resistant to medical therapy. METHOD: Sixteen women with CAAF without hypertonia of the internal anal sphincter, unresponsive to previous medical treatment, were included in the study. Absence of hypertonia was defined as a maximum anal resting pressure (MRP) of less than 85 mmHg. All patients underwent fissurectomy with an advancement skin flap. RESULTS: Complete healing occurred in all patients within 30 days. The intensity and the duration of pain after defecation reduced from the first postoperative defecation. MRP before surgery and at 6 months showed no significant difference. At 1 month, four patients experienced a continence disturbance, two of whom had it preoperatively. At 12 months, two (12.5%) patients continued to experience a continence disturbance. CONCLUSION: Fissurectomy with skin advancement flap resulted in complete healing and full relief of symptoms in all patients. There was a low incidence of continence disturbance.

[Bilateral testicular lymphoma. Case report]. / Linfoma primitivo testicolare bilaterale: a proposito di un caso clinico.

A case of bilateral testicular lymphoma with involvement of skin and oropharynx was described. After a review of literature, the Authors underline the clinical features focusing the diagnostic approaches and the therapeutics options.

Randomized clinical trial of botulinum toxin injection for pain relief in patients with thrombosed external haemorrhoids.

BACKGROUND: Thrombosed external haemorrhoids are one of the most frequent anorectal emergencies. They are associated with swelling and intense pain. Internal sphincter hypertonicity plays a role in the aetiology of the pain. This study evaluated the efficacy and safety of an intrasphincteric injection of botulinum toxin for pain relief in patients with thrombosed external haemorrhoids. METHODS: Thirty patients with thrombosed external haemorrhoids who refused surgical operation were randomized into two groups. Patients received an intrasphincteric injection of either 0.6 ml saline or 0.6 ml of a solution containing 30 units botulinum toxin. Anorectal manometry was performed before treatment and 5 days afterwards. RESULTS: After 5 days of treatment, the maximum resting pressure fell in both groups, but was significantly lower in the botulinum toxin group (P = 0.004). Pain intensity was significantly reduced within 24 h of botulinum toxin treatment (P < 0.001), but only after 1 week in the placebo group (P = 0.019). CONCLUSION: A single injection of botulinum toxin into the anal sphincter seems to be effective in rapidly controlling the pain associated with thrombosed external haemorrhoids, and could represent an effective conservative treatment for this condition. REGISTRATION NUMBER: NCT00717782 (http://www.clinicaltrials.gov).

Impact of different texture of polypropylene mesh on the inflammatory response.

Over the past decade, hernia surgery has undergone a considerable transformation with the use of prosthetic materials. The most used polypropylene meshes induce a rapid acute inflammatory response followed by chronic foreign body reaction. Many factors influence this response such as density, size, physical characteristics, different texture and porosity of each biomaterial. The aim of this study is to assess whether the implant of monofilament or multifilament meshes, in the inguinal hernioplasty, determine a different inflammatory response. Thirty-two male patients were included in the study and were randomly divided into two groups. In the first group (MO) inguinal hernioplasty was performed using monofilament polypropylene mesh, while in the second one (MU) multifilament prosthesis was used. Peripheral venous blood samples were collected 24 hours before surgery and then 6, 24, 48 and 168 hours post-operatively. Modifications in leukocyte count, C-reactive protein (CRP), alpha-1 antitrypsin (alpha1-AT), interleukin (IL)-1, IL-6, IL-1 ra and IL-10 serum levels were recorded at all sampling times. We present evidence that serum levels of CRP, (alpha1-AT), leukocytes and cytokines were significantly increased post-operatively in both groups, returning to basal values 168 hours afterwards. In particular, the production of all pro-inflammatory mediators was higher in the MU group, whereas the anti-inflammatory cytokine (IL-10, IL-1ra) production was higher in MO patients. Our results indicate that polypropylene multifilament mesh allows a higher intense acute inflammatory response as compared to monofilament mesh implantation.

Intramedullary spinal cord tumor presenting as the initial manifestation of metastatic colon cancer: case report and review of the literature.

STUDY DESIGN: Case reports and review of the literature. OBJECTIVE: Intramedullary spinal cord metastases (ISCMs) are rare type of central nervous system (CNS) involvement of systemic malignant tumors. Since the advent of new neuroradiological techniques, their detection have become increasingly diagnosed in recent years and, although somewhat controversial, surgical treatment has been considered a valid option. SETTING: Neurosurgical Clinic, Department of Clinic Neuroscience, University of Palermo, Italy. METHOD: The authors describe the case of a 61-year-old woman who was admitted presenting with progressive tetraplegia. Investigations revealed an intramedullary spinal cord lesion at the cervical level. Magnetic resonance imaging of the brain did not reveal other CNS metastatic lesions. RESULT: Patient underwent surgical treatment. The tumor was resected and the patient's neurologic deficits slowly improved. Histological examination of the lesion showed the typical features of a colon carcinoma metastasis. Patient was referred for proper oncological treatment but, unfortunately, she died of disseminated disease within 2 months. CONCLUSION: Although uncommon, spinal cord metastases should be considered in the differential diagnosis of ISCM in order to rationalize the decisional-making process and improve the quality of life for these patients.

Interferon-gamma mediated up-regulation of caspase-8 sensitizes medulloblastoma cells to radio- and chemotherapy.

Loss of caspase-8 expression - which has been demonstrated in a subset of Medulloblastoma (MB) - might block important apoptotic signalling pathways and therefore contribute to treatment resistance. In this study, IFN-gamma mediated up-regulation of caspase-8 in human MB cells was found to result in chemosensitization to cisplatin, doxorubicin and etoposide, and sensitisation to radiation. These effects were more prominent in D425 and D341 MB cells (low basal caspase-8 expression) when compared to DAOY MB cells (high basal caspase-8 expression). IFN-gamma mediated chemosensitization and radiosensitization effects were reduced by treatment with the caspase-8 specific inhibitor z-IETD-fmk. Treatment of IFN-gamma resulted in activation of STAT1 in DAOY MB cells and to a lesser extent in D425, but not in D341, indicating that IFN-gamma acts in MB cells through STAT1-dependent and -independent signalling pathways. Taken together, our results demonstrate that IFN-gamma mediated restoration of caspase-8 in MB cells might enhance apoptotic pathways relevant to the response to chemo- and radiotherapy.

Antisense treatment of IGF-IR induces apoptosis and enhances chemosensitivity in central nervous system atypical teratoid/rhabdoid tumours cells.

Central nervous system (CNS) atypical teratoid/rhabdoid tumours (AT/RT) are among the paediatric malignant tumours with the worst prognosis and fatal outcome. Insulin-like growth factor I receptor (IGF-IR) protects cancer cells from apoptosis induced by a variety of anticancer drugs and radiation. In the present study, IGF-IR was expressed in 8/8 primary AT/RT as detected by immunohistochemistry. Moreover, we found IGF-I and IGF-II mRNA in BT-16 CNS AT/RT cells and IGF-II mRNA in BT-12 CNS AT/RT cells, and autophosphorylated IGF-IR in both cell lines, indicating the potential presence of an autocrine/paracrine IGF-I/II/IGF-IR loop in CNS AT/RT. IGF-IR antisense oligonucleotide treatment of human CNS AT/RT cells resulted in significant down-regulation of IGF-IR mRNA and protein expression, induction of apoptosis, and chemosensitisation to doxorubicin and cisplatin. These studies provide evidence for the influence of IGF-IR on cellular responses to chemotherapy and raise the possibility that curability of selected CNS AT/RT may be improved by pharmaceutical strategies directed towards the IGF-IR.

Use of fibrin glue in the treatment of pilonidal sinus disease: a pilot study.

BACKGROUND: Pilonidal sinus (PS) disease of the sacrococcigeal region is an acquired condition resulting from penetration of shed hair shafts through the skin. Different types of operations have been described in the letterature. More recently fibrin glue has been used with succesfull. Aim of this study was to assess the effectiveness of fibrin glue for the treatment of pilonidal sinus. PATIENTS AND METHODS: Eight patients age ranged 21,8 +/- 6,5 affected by PS disease of sacrococcigeal region were included in this study. All patients undergoing surgical operation under local anaesthesia. Following administration of 1% methylene blue through the main opening, a small vertical elliptical incision is maked including the entire sinus opening and an excision of PS was performed without entering the sinus cavity, removing a minimal amount of subcutaneous tissue. Afterwards the highly concentrated fibrin glue, containing 1,000 U/ml of thrombin was applied to cover the wound. Post-operative pain, analgesic consumption, duration of hospital stay, failure healing, the rate and time of recurrence, time to healing, time to return to work and post-operative complications were recordered. RESULTS: All patients expressed satisfaction with the procedure. Mean hospital stay was 5.4 +/- 2.1 hours. Healing was achieved after 25.8 +/- 13.2 days. The post-operative pain mean score was 3.8 +/- 2.1 in first day, 2,9 +/- 1,8 in third day and 1,3 +/- 0,8 in the seventh day. The mean analgesic consumption per week was 5,6 +/- 3,2 medications. Mean time to return to work was 5,3 +/- 2,1 days. CONCLUSION: The minimal excision of PS and application of fibrin glue is a non-invasive effective treatment, easy and simple to performe and not associated to recurrences. For these reasons this procedure in our opinion as the first line treatment for pilonidal sinus disease.

Production of cytokines at the operation site.

BACKGROUND AND AIM: Cytokines are part of a family of molecules involved in the initiation, control and termination of the events that occurs in wound healing process. Aim of this study was to evaluate the production of some cytokines [interleukin (IL)-6, IL-10, IL-1alpha, IL-1ra, interferon (IFN)-gamma] in the drainage wound fluid from patients undergoing incisional hernia repair. METHODS: Ten female patients with abdominal midline incisional hernia undergoing to surgical repair were included in this study. In all cases a closed suction drain was placed in the wound below the fascia and it was removed on the 4th postoperative day. Wound fluid was collected on the 1st, 2nd, 3rd and 4th day and its amount in each time was recorded. The production of IL-6, IL-10, IL-1alpha, IL-1ra and IFN-gamma were evaluated as quantity produced in 24 hour. RESULTS: In all patients the amount of drain fluid from surgical wound was highest on the 1st day after surgery, afterwards there is a significant reduction. The production of all cytokines evaluated was highest on the 1st day decreasing on the 2nd day except for IL-1alpha that not show any modification. The produciton of IL-1ra, IL-6, IL-1alpha and IL-10 was significantly reduced on the 3rd and 4th postoperative day in comparison with the respectively values recorded on the 1st day, whereas IFN-gamma levels were similar. CONCLUSIONS: The dosage of cytokines in the drain fluid led us to better evaluated the events that follow surgical wound and their analysis offers further information in the role of cytokines in healing process, with the goal to get supportive treatments to promote the best evolution.

[Jejunal cystic lymphangioma in adult with rapid growth]. / Linfangioma cistico del digiuno a rapida crescita nell'adulto.

Abdominal cystic lymphangiomas are a rare pathology that are related to abnormal development of the lymphatic system. They predominate in a children and are very uncommon in adults. Here the authors report a case of a cystic intra-abdominal lymphangioma in a 64-years old woman in which the cyst was situated in the mesentery of the jejuneum, with rapid growth. Ultrasonography, computed tomography and magnetic resonance imaging led us to evaluate a cystic characterizations and his site. Surgical excision remain the treatment of choice because we can establish an histologic diagnosis. Complete surgical excision of cyst, although it can be difficult, consent a definitive healing.

[Free perforation in Crohn's disease]. / La perforazione in peritoneo libera nella malattia di Crohn.

Free perforation in abdominal cavity in patients with Crohn's disease is a rare entity as attested from the data reported in the literature. It is a very dangerous event and requires a surgical urgency management. The Authors reported two cases of free perforation, in patients with Crohn' disease, undergoing surgical operation in urgency. Analyzing pathogenesis, difficulty in diagnosis making and therapeutic choices, they underline that CT is very useful in the diagnosis, while resection of the perforated intestinal tract represent the best surgical treatment.

[Milligan-Morgan haemorrhoidectomy with ultrasonic scalpel]. / L'emorroidectomia secondo Milligan-Morgan con bisturi ad ultrasuoni.

INTRODUCTION: Milligan-Morgan haemorrhoidectomy is considered the best treatment for hemorrhoidal disease. Although this, many patients complaint post-operative pain that remain the worse complication. For this reason different are the trials performed in order to reduce his intensity. In this report we want to evaluate if the use of ultrasonic scalpel to perform Milligan-Morgan hemorrhoidectomy, compared with conventional surgery, could reduce post-operative pain. MATERIALS AND METHODS: 30 patients with III and IV degree of haemorrhoids were included in this study and divided in two groups. In the first group Milligan-Morgan haemorrhoidectomy was performed with conventional instruments, while in the second group the some procedure was performed with ultrasonic scalpel. The duration of intervention, time hospitalization, the time to open alvus to stools, the time to return to normal activity, the complications, pain and the amount of analgesic consumption were evaluated. RESULTS: In the II group's patients, it was observed a reduced time to healing with reduced spread of necrosis and inflammatory pattern, associated with reduced post-operative pain and the lower analgesic consumption. CONCLUSIONS: The use of ultrasonic scalpel to perform Milligan-Morgan haemorrhoidectomy, compared with conventional instruments, reduce post-operative pain making a more short time to healing and a precocious time to return to normal activity. For this reason we believe that the use of ultrasonic scalpel, although a more elevated costs, seems to be advantageous.

Role of MAP kinase pathways in primitive neuroectodermal tumors.

Mitogen-activated protein kinase and Phosphatidylinositol-3 kinase/Akt-mediated signaling pathways play a major role in controlling cell proliferation, differentiation and cell death. Phosphorylation and dephosphorylation of their specific Thr/Tyr residues is critical in determining their activity. We determined the expression pattern and activity of MAP kinases and Akt in Primitive Neuroectodermal Tumors (PNETs). The kinase activity of extracellular signal-regulated kinase (ERK) was higher in both primary tumors and cell lines, as evident from the increased phosphorylation of ERK1 and ERK2. We did not observe the activation of C-jun N-terminal kinase (JNK) or p38 MAPK The expression of Raf-1, a kinase acting upstream of ERK, was significantly increased in primary tumors compared to normal brain. The PI-3 kinase-activated phosphorylation of Akt was also higher in primary tumors. These results suggest that activation of the Raf-1/ERK module of the MAP kinase pathway play an important role in PNETs.

Cytokine modifications after tension-free hernioplasty or open conventional inguinal hernia repair.

BACKGROUND: The purpose of this study was to evaluate the involvement of proinflammatory cytokines (interferon-gamma [INF-gamma], interleukin [IL]-6) and anti-inflammatory cytokines (IL-4, IL-l0, IL-13) in patients undergoing Lichtenstein tension-free hernioplasty (LH) using polypropylene prosthetic materials or conventional Bassini hernia (BH) repair. METHODS: Thirty-five male patients (age range 25 to 60 years) with unilateral inguinal hernia without complications or recurrence were included in this study. Randomly, patients underwent conventional operation and had their inguinal hernia repair performed with polypropylene mesh. Peripheral venous blood samples were collected 24 hours prior to surgery and then 6, 24, 48, and 168 hours postoperatively. Fifteen healthy controls were included. RESULTS: We present evidence that LH patients showed both an increased serum level of Thelper 1 (Th1)-like cytokines (IFN-gamma) and an increase in Thelper 2 (Th2)-like cytokines (IL-6 and IL-l0), associated with a slight reduction of peripheral blood mononuclear cells (PBMC) producing IL-6 and a normal level of PBMC producing IFN-gamma, IL-l0, IL-13, and IL-4. Whereas BH patients showed in part an amplification of Th2-like cells, characterized by the sustained serum production of IL-6 and IL-l0, associated with an increase in IL-l0 secreted by in vitro stimulated PMBC. CONCLUSIONS: Our data show that LH is associated with a higher production of inflammatory cytokines (IFN-gamma and IL-6) compared with BH, likely induced by the presence of the polypropylene prostheses.

99mTc labeled VIP analog: evaluation for imaging colorectal cancer.

Early and reliable diagnosis of colorectal cancer continues to be demanding and challenging. Colorectal cancer cells express Vasoactive Intestinal Peptide (VIP) receptors in high density. We have prepared a VIP analog (TP3654), labeled it with (99m)Tc, and evaluated it in experimental animals as an agent for imaging colorectal cancer. The tissue distribution of (99m)Tc-TP3654 has been compared with that of (111)In-DTPA-Octreotide and (99m)Tc-anti-CEA scan in nude mice bearing human colorectal cancer LS174T. Finally, pharmacokinetic and tissue distribution studies of (99m)Tc-TP3654 have been performed in four normal human volunteers. Data suggest that (99m)Tc-TP3654 can be prepared efficiently without loss of its receptor specificity and biological activity. Although the 24 hr tumor uptake of (99m)Tc-TP3654 in the animal model used was modest (0.21 +/- 0.07% I.D./g), the tissue distribution profile was more favorable than that of (111)In-DTPA-Octreotide or (99m)Tc-anti-CEA scan. Human studies indicated that (99m)Tc-TP3654 had no adverse effect in any subject. Within 24 hours, approximately 70% of the injected dose cleared through the kidneys, and approximately 20% through the hepatobiliary system. In these non-fasting volunteers hepatobiliary clearance was slow and in cancer patients tumor uptake was rapid. Data suggest that (99m)Tc-TP3654 is a promising agent for imaging colorectal cancer.